Bottom Line:
We then wondered whether a similar response was observed in the subsequent generation.A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached.Further well powered studies are warranted to validate the latter finding.

ABSTRACTIn a previous study, we demonstrated that mouse adult F(1) offspring, exposed to a vitamin D deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F(2) females whose F(1) parents (males or females) were vitamin D-deprived when developing in the uterus of F(0) females. Unexpectedly, we observed that the vitamin D deficiency affecting the F(0) pregnant mice induced a precocious and more severe EAE in the F(2) generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents' dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin D status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.

f1-ijms-13-10911: Schematic view of the experimental model. All mice, except F0 females, were fed with a standard vitamin D-containing mouse chow. F0 females were vitamin D-deprived six weeks prior mating and maintained on a deficient diet during pregnancy. F1 DVD-deficient offspring, females and males, were mated with control mice. Only F2 female offspring were subjected to Experimental Autoimmune Encephalomyelitis (EAE).

Mentions:
Though paradoxical, the response of the first generation to the EAE model suggests that a transient maternal hypovitaminosis D results in an altered immune response after exposure to the myelin-related protein. It remained however to be seen whether this environment-related change could be associated with any altered immune-related phenotype in the subsequent generation, as has been previously demonstrated in rats exposed to a fungicide [17]. We wondered if the second generation (F2) had any persisting alterations in immune function related to the vitamin D status of the pregnant F0 female mice. With the aim of exploring this hypothesis, we designed a new experimental model, schematized in Figure 1.

f1-ijms-13-10911: Schematic view of the experimental model. All mice, except F0 females, were fed with a standard vitamin D-containing mouse chow. F0 females were vitamin D-deprived six weeks prior mating and maintained on a deficient diet during pregnancy. F1 DVD-deficient offspring, females and males, were mated with control mice. Only F2 female offspring were subjected to Experimental Autoimmune Encephalomyelitis (EAE).

Mentions:
Though paradoxical, the response of the first generation to the EAE model suggests that a transient maternal hypovitaminosis D results in an altered immune response after exposure to the myelin-related protein. It remained however to be seen whether this environment-related change could be associated with any altered immune-related phenotype in the subsequent generation, as has been previously demonstrated in rats exposed to a fungicide [17]. We wondered if the second generation (F2) had any persisting alterations in immune function related to the vitamin D status of the pregnant F0 female mice. With the aim of exploring this hypothesis, we designed a new experimental model, schematized in Figure 1.

Bottom Line:
We then wondered whether a similar response was observed in the subsequent generation.A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached.Further well powered studies are warranted to validate the latter finding.

ABSTRACTIn a previous study, we demonstrated that mouse adult F(1) offspring, exposed to a vitamin D deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F(2) females whose F(1) parents (males or females) were vitamin D-deprived when developing in the uterus of F(0) females. Unexpectedly, we observed that the vitamin D deficiency affecting the F(0) pregnant mice induced a precocious and more severe EAE in the F(2) generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents' dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin D status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.